DESCRIPTION: This represents a revised application (albeit with a new number) from an established investigator, Dr. Donald Nuss, currently Professor and Director at the Center for Agricultural Biotechnology of the University of Maryland. Largely through Dr. Nuss's work, it has been found that the prototypic member of the RNA virus family, poviridae, persistently alters phenotypic traits and attenuates virulence of its pathogenic fungal host, primarily by disrupting cellular G-protein-linked signal transduction. Thus hypoviruses provide utility as biocontrol agents and as tools for identifying fungal virulence determinants and antimycotic therapeutic agents. A major advance in this field came from Dr. Nuss s development of an infectious hypovirus cDNA clone and infectious transcripts, making the virus amenable to genetic analysis. Major future goals include a fundamental analysis of hypovirus molecular biology and an understanding of the mechanisms by which hypoviruses persistently alter host phenotype. The aims of this proposal are: (i) To further characterize hypovirus polyprotein processing. This will extend work which revealed that the viral protease p29 was a determinant of viral mediated alteration of fungal phenotype. (ii) To extend functional mapping of hypovirus coding domains. (iii) To extend the understanding of mechanisms underlying hypovirus mediated alteration of G protein signal transduction. (iv) Finally, to investigate mechanisms by which a known hypovirus symptom determinant, p29, alters host phenotype.